Role of dihydrotestosterone in androgen action

Androgen action differs from that of most hormones in that testosterone, the major androgen secreted from the testes and the most abundant androgen in the circulation of men, is not the principal androgen within target cells. Indeed, abundant evidence indicates that most androgen actions are mediated by the 5α-reduced metabolite dihydrotestosterone that is formed in target tissues. The conversion of testosterone to dihydrotestosterone is mediated by two isoenzymes; mutations in the steroid 5α-reductase 2 gene cause a rare autosomal-recessive form of male pseudohermaphroditism, and inhibition of this enzyme causes regression of the prostate gland. Dihydrotestosterone binds more tightly to the androgen receptor than does testosterone, but it is not clear whether this property is the sole explanation for its essential role in androgen action. Nor is it clear whether some androgenic effects may be mediated by circulating dihydrotestosterone acting as a hormone.